Medaka as a model system for the characterisation of cell cycle regulators: a functional analysis of Ol-Gadd45gamma during early embryogenesis
| Autor: | Jean-Stéphane Joly, Violette Thermes, Eva Candal, Franck Bourrat |
|---|---|
| Přispěvatelé: | Développement, évolution et plasticité du système nerveux (DEPSN), Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie Alfred Fessard (INAF), USC CNRS jeune équipe Développement, Evolution et Plasticité du Système Nerveux (DEPSN), Institut National de la Recherche Agronomique (INRA) |
| Rok vydání: | 2004 |
| Předmět: |
Embryology
Morpholino Oryzias [SDV]Life Sciences [q-bio] Proliferation Apoptosis MESH: Cell Cycle MESH: Flow Cytometry MESH: Amino Acid Sequence Gadd45γ mRNA misexpression 0302 clinical medicine MESH: Animals MESH: Proteins CR6 MESH: Phylogeny Phylogeny 0303 health sciences Gadd45 Neurogenesis Cell Cycle MESH: DNA Intracellular Signaling Peptides and Proteins Embryo Cell cycle Flow Cytometry Cell biology [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] DNA damage Molecular Sequence Data Cell fate determination Biology 03 medical and health sciences MESH: Gene Expression Profiling MESH: Intracellular Signaling Peptides and Proteins BIOLOGIE DU DEVELOPPEMENT Animals [INFO]Computer Science [cs] Expression pattern Amino Acid Sequence 030304 developmental biology MESH: Molecular Sequence Data Gene Expression Profiling Proteins DNA biology.organism_classification Medaka MESH: Oryzias Cell cycle regulation 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Mechanisms of Development Mechanisms of Development, Elsevier, 2004, 121 (7-8), pp.945-58. ⟨10.1016/j.mod.2004.03.007⟩ Mechanisms of Development, Elsevier, 2004, 121 (7-8), pp.945-958 |
| ISSN: | 0925-4773 |
| DOI: | 10.1016/j.mod.2004.03.007⟩ |
| Popis: | Numerous studies, mostly performed on mammalian cell cultures, have implicated the Gadd45 family of small acidic proteins in cell cycle control (arrest and/or engagement in the apoptotic pathway). We report here the cloning, detailled expression pattern and functional characterisation in embryonic development of Ol-Gadd45gamma, the Oryzias latipes ortholog of mammalian Gadd45gamma. Its expression pattern, notably in the developing brain (optic tectum) strongly suggests that it is involved in cell cycle exit. Gain-of-function experiments (through mRNA injection) slowed down early development, and produced embryos clearly reduced in size, while morpholino knockdowns resulted in small embryos over-sensitive to DNA damage (UV irradiation). We further demonstrated that, following Ol-Gadd45gamma overexpression, cells are proliferation-arrested before both G1/S and G2/M cell cycle checkpoints, while in the MO-Ol-Gadd45 loss-of-function experiments cells are engaged in apoptosis rather than prevented from proliferating. These results show that Ol-Gadd45gamma is likely to play an important role in coordinating cell fate decisions during neurogenesis; they also demonstrate that the medakafish is a promising model to analyse in vivo the developmental control of the cell cycle. |
| Databáze: | OpenAIRE |
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